Development of a Novel Inflammatory Index to Predict Coronary Artery Disease Severity in Patients With Acute Coronary Syndrome.

The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have previously demonstrated predictive value in coronary artery disease (CAD). We developed on an expanded, novel systemic immune-inflammation response index (SIIRI), calculated as peripheral neutrophil × monocyte × platelet ÷ lymphocyte count. We assessed 240 patients with an acute coronary syndrome that subsequently underwent percutaneous coronary intervention. CAD severity was measured using the SYNTAX score. Laboratory measurements, including cell counts, were obtained on admission. On multivariate analysis, the SIIRI was an independent predictor of severe CAD with an adjusted odds ratio (OR) of 1.666 [1.376-2.017] per 105-unit increase. The SIIRI had the highest area under the receiver operator curve of .771 [.709-.833] compared to the SII, SIRI neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio. The optimal cut-off for SIIRI was 4.3 × 105, with sensitivity = 69.9% and specificity = 75.8%. Increment in model performance resulting from adding SIIRI versus other inflammatory indices was assessed using discrimination, calibration, and goodness-of-fit measures. When added to a baseline model, the SIIRI resulted in a significant increase in the c-statistic and significant net reclassification index (.808, P < .0001) and integrated discrimination index (.129, P < .0001), and a decrease in Akaike and Bayesian information criteria.

Combined nutritional and frailty screening improves assessment of short-term prognosis in older adults following percutaneous coronary intervention.

BACKGROUND: Frailty and malnutrition are well-known factors influencing outcomes of myocardial infarction (MI) in older adults. Due to considerable overlap between both entities, whether the simultaneous assessment of frailty and nutrition adds nonredundant value to risk assessment is unknown. METHODS: We performed a prospective cohort study on 402 patients aged at least 65 years diagnosed with ST-elevation MI that underwent percutaneous coronary intervention. Nutritional status was assessed by Controlling Nutritional Status score (CONUT), Prognostic Nutritional Index, and Geriatric Nutritional Response Index. Frailty was assessed by Clinical Frailty Scale (CFS), Derby frailty index, and acute frailty network. Primary outcome was major adverse cardiac events (MACE), comprising all-cause mortality, non-fatal MI, and unplanned repeat revascularization during 28-day follow-up. Increment in Global Registry of Acute Coronary Events (GRACE) score performance following the addition of nutrition and frailty was assessed. RESULTS: The incidence of MACE was 8.02 (6.38-9.95) per 1000 person-days. The CONUT score and CFS were the best predictors of MACE and independent predictors in the multivariate Cox-regression models [hazard ratios, 2.80 (1.54-5.09) and 2.54 (1.50-4.29)]. CONUT score classified 151 (37.6%) patients as malnourished, and CFS classified 131 (32.6%) as frail. The addition of both CONUT and CFS to the GRACE score led to better model discrimination and calibration through improved c-statistic (+0.165) ( P < 0.0001) and Akaike and Bayesian information criteria. CONCLUSION: Combining CONUT and CFS provides nonredundant prognostic value despite their overlapping nature. Combined nutritional and frailty screening may improve risk prognostication in older adults following MI.

The systemic immune-inflammation index in predicting sepsis mortality.

BACKGROUND: The systemic immune-inflammation index (SII) is a novel parameter and its role in the prognosis of sepsis has never been explored previously. METHODS: We retrospectively assessed 267 patients with blood-culture confirmed sepsis. Clinical and laboratory data recorded at intensive care unit (ICU) admission were analyzed. Outcomes of interest included in-hospital mortality and length-of-stay (LOS) in the ICU. Sequential Organ Failure Assessment (SOFA) scores, SII, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. Multivariable regression analysis was used to identify independent predictors of LOS and mortality. Area under receiver operator characteristic (AUROC) curves were used to determine optimum cutoffs, and the incremental effect of SII on the SOFA score was assessed using model discrimination and calibration properties. RESULTS: There were 76 (28.5%) non-survivors. SII, NLR, and PLR were independent predictors of sepsis mortality, with adjusted odds ratios of 1.51 (1.24-1.84), 1.67 (1.30-2.13) and 1.24 (1.11-1.39). SII and SOFA score were independent predictors of LOS. SII had an AUROC of 0.848, and the optimum cutoff was 564 with a sensitivity and specificity of 85.5% and 71.2%. The addition of SII to the model had a significant incremental effect on the predictive ability of SOFA score (Net Reclassification Index = 0.084, P = 0.025; Integrated Discrimination Index = 0.056, P = 0.001). CONCLUSION: The SII is an inexpensive parameter that can be used in addition to clinical sepsis scores to improve the accuracy of patient assessment.

Perception without preconception: comparison between the human and machine learner in recognition of tissues from histological sections.

Deep neural networks (DNNs) have shown success in image classification, with high accuracy in recognition of everyday objects. Performance of DNNs has traditionally been measured assuming human accuracy is perfect. In specific problem domains, however, human accuracy is less than perfect and a comparison between humans and machine learning (ML) models can be performed. In recognising everyday objects, humans have the advantage of a lifetime of experience, whereas DNN models are trained only with a limited image dataset. We have tried to compare performance of human learners and two DNN models on an image dataset which is novel to both, i.e. histological images. We thus aim to eliminate the advantage of prior experience that humans have over DNN models in image classification. Ten classes of tissues were randomly selected from the undergraduate first year histology curriculum of a Medical School in North India. Two machine learning (ML) models were developed based on the VGG16 (VML) and Inception V2 (IML) DNNs, using transfer learning, to produce a 10-class classifier. One thousand (1000) images belonging to the ten classes (i.e. 100 images from each class) were split into training (700) and validation (300) sets. After training, the VML and IML model achieved 85.67 and 89% accuracy on the validation set, respectively. The training set was also circulated to medical students (MS) of the college for a week. An online quiz, consisting of a random selection of 100 images from the validation set, was conducted on students (after obtaining informed consent) who volunteered for the study. 66 students participated in the quiz, providing 6557 responses. In addition, we prepared a set of 10 images which belonged to different classes of tissue, not present in training set (i.e. out of training scope or OTS images). A second quiz was conducted on medical students with OTS images, and the ML models were also run on these OTS images. The overall accuracy of MS in the first quiz was 55.14%. The two ML models were also run on the first quiz questionnaire, producing accuracy between 91 and 93%. The ML models scored more than 80% of medical students. Analysis of confusion matrices of both ML models and all medical students showed dissimilar error profiles. However, when comparing the subset of students who achieved similar accuracy as the ML models, the error profile was also similar. Recognition of 'stomach' proved difficult for both humans and ML models. In 04 images in the first quiz set, both VML model and medical students produced highly equivocal responses. Within these images, a pattern of bias was uncovered-the tendency of medical students to misclassify 'liver' tissue. The 'stomach' class proved most difficult for both MS and VML, producing 34.84% of all errors of MS, and 41.17% of all errors of VML model; however, the IML model committed most errors in recognising the 'skin' class (27.5% of all errors). Analysis of the convolution layers of the DNN outlined features in the original image which might have led to misclassification by the VML model. In OTS images, however, the medical students produced better overall score than both ML models, i.e. they successfully recognised patterns of similarity between tissues and could generalise their training to a novel dataset. Our findings suggest that within the scope of training, ML models perform better than 80% medical students with a distinct error profile. However, students who have reached accuracy close to the ML models, tend to replicate the error profile as that of the ML models. This suggests a degree of similarity between how machines and humans extract features from an image. If asked to recognise images outside the scope of training, humans perform better at recognising patterns and likeness between tissues. This suggests that 'training' is not the same as 'learning', and humans can extend their pattern-based learning to different domains outside of the training set.

Atherogenic index of plasma predicts coronary artery disease severity and major adverse cardiac events in absence of conventional risk factors.

BACKGROUND: Various overlapping risk factors lead to coronary artery disease (CAD). The atherogenic index of plasma (AIP) is a marker for CAD severity and progression. However, little is known about its contribution to the residual risk of CAD observed in the absence of all typical risk factors. METHODS: A prospective cohort study of 366 Indian patients undergoing coronary computed tomography (CT) angiography and diagnosed with stable CAD. Diabetes, hypertension, hypercholesterolemia, smoking, previous CAD, alcohol or lipid-lowering medication intake, renal, liver or thyroid dysfunction were exclusion criteria. Coronary stenosis was graded using the CAD-reporting and data system (CAD-RADS™) system. Lipid profile, HbA1c, uric acid, highly sensitive C-reactive protein (hsCRP) and anthropometric measurements were taken. AIP, triglyceride/high-density lipoprotein cholesterol (HDLc) and total cholesterol (Tc)/HDLc ratios were calculated. Independent predictors of CAD severity and the occurrence of major adverse cardiac events (MACE) during 2.57 (0.52) years of follow-up were identified using logistic regression and Cox proportional hazards regression. RESULTS: Sixty patients experienced a MACE during a cumulative 887.03 person-years. HbA1c, uric acid, hsCRP, Tc/HDLc and AIP were independent predictors of severe coronary lesions (CAD-RADS 4,5) on multivariate analysis with odds ratio 4.52 (2.37-8.61), 1.41 (1.08-1.84), 1.33 (1.09-1.62), 1.76 (1.27-2.44) and 1.29 (1.11-1.50), respectively. Only AIP and Tc/HDLc were independent predictors of MACE with hazard ratios of 1.41 (1.20-1.65) and 1.78 (1.33-2.39) besides patient age and CAD severity. CONCLUSION: AIP is associated with both the severity of CAD and the occurrence of MACE within 3 years. It could serve as an effective marker of residual risk of CAD in patients devoid of traditional risk factors. Lipid-profile ratios, such as AIP are cost-effective and accessible parameters suitable for low and middle-income settings.

Sleep, Cognition, and Yoga.

Stress is one of the major problems globally, associated with poor sleep quality and cognitive dysfunction. Modern society is plagued by sleep disturbances, either due to professional demands or lifestyle or both the aspects, often leading to reduced alertness and compromised mental function, besides the well documented ill effects of disturbed sleep on physiological functions. This pertinent issue needs to be addressed. Yoga is an ancient Indian science, philosophy and way of life. Recently, yoga practice has become increasingly popular worldwide. Yoga practice is an adjunct effective for stress, sleep and associated disorders. There are limited well controlled published studies conducted in this area. We reviewed the available literature including the effect of modern lifestyle in children, adolescents, adults and geriatric population. The role of yoga and meditation in optimizing sleep architecture and cognitive functions leading to optimal brain functioning in normal and diseased state is discussed. We included articles published in English with no fixed time duration for literature search. Literature was searched mainly by using PubMed and Science Direct search engines and critically examined. Studies have revealed positive effects of yoga on sleep and cognitive skills among healthy adults as well as patients of some neurological diseases. Further, on evaluating the published studies, it is concluded that sleep and cognitive functions are optimized by yoga practice, which brings about changes in autonomic function, structural changes, changes in metabolism, neurochemistry and improved functional brain network connectivity in key regions of the brain.

Platelet Indices and Their Kinetics Predict Mortality in Patients of Sepsis.

Platelet indices are inexpensive, easily accessible parameters and potentially useful prognostic indicators in sepsis. In this study we explore the differences in platelet indices and their kinetics between sepsis survivors and non-survivors. A retrospective cohort-study of 97 cases of culture-positive sepsis at a tertiary-care center in North India. Demographics, clinical and laboratory parameters at admission were assessed. Platelet count (PLT), mean-platelet-volume (MPV), platelet-distribution-width (PDW) and plateletcrit (PCT) on admission, and third, fifth and last days of hospitalization were analyzed. Fractional change in platelet indices (ΔMPV72h, ΔPDW72h, ΔPCT72h, and ΔPLT72h) by day-3 were calculated. Unpaired and paired t-tests were used to compare survivors with non-survivors, and to study the change in platelet indices with time. Logistic regression was used for multivariate analysis. ROC-curves and optimum cut-offs to predict mortality were obtained. There were 64 survivors. Non-survivors had significantly higher ΔMPV72h, ΔPDW72h, day-1 MPV and PDW, and lower ΔPLT72h. MPV and PDW increased, and PLT decreased with time among non-survivors. Trends were reversed in survivors. Only MPV and PDW showed significant change by day-3. Both were independent predictors of mortality on multivariate analysis, alongside ΔMPV72h and ΔPLT72h. On ROC analysis, MPV, PDW, ΔMPV72h, ΔPDW72h and ΔPLT72h effectively predicted mortality. Cut-off for MPV was 10.25 fL (sensitivity = 93.9%, specificity = 60.9%), and PDW, 12.6% (sensitivity = 84.8%, specificity = 51.6%). A rise in MPV and a fall in PLT was associated with mortality in this study. MPV and PDW values at admission are effective predictors of mortality and may be used in conjunction with traditional parameters.

Symptomatic CSF HIV Escape in Patients on Anti Retroviral Therapy - A Case Series from India.

The central nervous system is believed to be a safe sanctuary site which is established very early in the course of HIV infection where the virus can escape antiretroviral therapy. HIV associated neurocognitive disorder (HAND) is seen to occur even in patients on successful systemic ART. HIV RNA can be at higher levels in CSF than plasma termed as CSF / plasma discordance or CSF escape. We aimed to study the prevalence, risk factors and outcomes in HIV patients who develop neurocognitive dysfunction on otherwise successful (suppressive) ART. We reported 6 cases of HAND in patients on regular successful ART over a 3 year period. Neurological examination , CSF analysis , plasma CD4 T cell count and neuroimaging were done.. Plasma HIV RNA and CSF HIV RNA was also estimated. Most of the patients' (5/6) were male, median age was 38.5 years and median time since HIV diagnosis was 3 years. All patients' were on Tenofovir plus Boosted Protease inhibitors when neurocognitive symptoms were manifest. 4/6 patients had an acute onset of clinical presentation. CSF showed elevated protein and mild pleocytosis in all patients. Median nadir CD4 T cell count was 222 cells / µl and at presentation of HAND with CSF escape was 374 cells / µl. CSF / Plasma HIV RNA discordance was present in all patients' at time of diagnosis. Outcome is good if diagnosed and treated early.

The Study of MIB-1 LI and CD 34 As A Marker of Proliferative Activity and Angiogenesis in Different Grades of Meningioma.

INTRODUCTION: Meningiomas comprise 24-30% of all tumours occurring in the central nervous system. Conventional morphologic critera as studied in routine Haematoxylin and Eosin stained sections (H & E) may not be accurate in grading and assessing prognosis in small stereotactic biopsy specimens. Thus, arises the need for objective methods for assessing tumour biology. Angiogenesis is a key event in the spread of tumours and denotes a poor prognosis. Intratumoural Microvessel Density (MVD) helps in quantification of angiogenesis. AIM: To measure the proliferative index by MIB-1 and correlate it with the WHO grading of meningiomas. Also to assess the expression of CD34 in various grades of meningioma and evaluate their angiogenic potential by calculating MVD. MATERIALS AND METHODS: Paraffin blocks of 30 surgically resected cases, 10 each of grade I, II and III meningiomas were reviewed. Tumours were graded and subtyped as per WHO criteria. Immunohistochemical staining was done with MIB-1 and CD 34 antibodies. Statistical analysis was performed using Mann - Whitney U test. p-value of < 0.05 was considered significant. RESULTS: The male to female ratio overall was 1:1. The age of the patients ranged from 18-81 years. A 73% of patients had raised intracranial pressure and 18.4% of patients presented with seizures. The mean ± SD MIB-1 LI was 1.14 ± 0.84, 8.94 ± 2.73 and 35.62 ± 4.44 in grade I, II and III tumours respectively which was statistically significant. (p< 0.01). The mean ± SD MVD was 49.67 ± 22.35, 41.37 ± 7.45 and 47.86 ± 10.77 respectively in grade I, II and III tumours (p NS). CONCLUSION: MIB-1 LI is an important complementary tool to accurately grade meningothelial tumours and assess tumour biology. Specific cycling endothelial markers along with CD 34 & MVD could be used to assess the prognosis of these tumours.

Xanthogranulomatous endometritis presenting as pyometra and mimicking carcinoma on imaging.

Xanthogranulomatous endometritis (XGE) is an uncommon but well-established histopathological entity seen affecting the kidney and gallbladder. Involvement of the endometrium is very rare, with only a few case reports in world literature till date. Histologically, it is characterized by the replacement of the endometrium by sheets of foamy histiocytes, plasma cells, lymphocytes, giant cells, and siderophages. We present a case of a 74-year-old female who presented with foul-smelling discharge and postmenopausal bleeding of a short duration. Clinical examination and imaging studies revealed a pyometra, cervical stenosis. A suspicion of carcinoma was raised. Since XGE may mimic an endometrial carcinoma clinically and pathologically, knowledge of this unusual and rare inflammatory pathology is important for both the gynecologists and the pathologists.

Nevus Lipomatosis Cutaneous Superficialis - A clinicopathologic study of the solitary type.

BACKGROUND: Nevus Lipomatosis Cutaneous Superficialis (NLCS) is a rare, benign hamartomatous lesion characterized by the ectopic presence of mature adipocytes in the reticular dermis not associated with the underlying subcutaneous tissue. Two clinical forms-classical and solitary occur. The solitary form is relatively uncommon, due to which these lesions are commonly clinically misdiagnosed. The aim was to study the clinical and histopathological features of the solitary type of NLCS. METHODS: Seven cases of histopathologically documented solitary type of NLCS which presented at our institute between August 2013 and June 2014 were retrospectively analysed for clinical data and histopathological findings. Haematoxylin and Eosin (H&E) and Elastic Van Gieson (EVG) stained slides were studied in all cases. RESULTS: Mean age of the patients was 42.5 years. These lesions were more common in adult females (5/7). Thigh was the commonest location (4/7). The mean duration of these lesions was 2.0 years. Clinical diagnosis was papilloma (4/7) and acrochordon (3/7). Histopathology revealed the presence of varying amounts of mature ectopic adipocytes in the dermis located around dilated, ectactic blood vessels. Disorganised dermal collagen bundles and atrophic pilosebaceous units were seen. CONCLUSION: This study is a first from the Indian subcontinent and highlights the need for awareness of this rare clinical condition both by the dermatologists and the surgeons. Histopathology is essential for diagnosis as clinically they may mimic papillomas or skin tags. An early diagnosis may permit a more conservative resection of the tumour.

Paragonimus westermani infection in lung: A confounding diagnostic entity.

Paragonimiasis is a food-borne parasitic zoonosis caused by the genus Paragonimus. Fresh water snails, crabs, and crayfish are the first and second intermediate hosts, respectively. Humans acquire this infection by ingesting uncooked/undercooked crustaceans. Laboratory diagnosis of Paragonimiasis is done by demonstration of ova in the sputum/feces/pleural fluid or by serology. A case of pulmonary Paragonimiasis is presented herewith; the patient having been diagnosed with pulmonary tuberculosis earlier. The aim of this presentation is to highlight this entity so that it is considered in the differential diagnosis in a case of hemoptysis.

Pseudohyperplastic variant of adenocarcinoma as a component of α-methyl-CoA-racemase (AMACR negative) carcinosarcoma of the prostate.

Carcinosarcoma (CS) or Sarcomatoid carcinoma (SC) of the prostate is a very rare malignant tumor of the prostate having an aggressive clinical course and dismal prognosis. The adenocarcinomatous element is usually of the acinar type and closely admixed with a sarcomatous component. We report a case of α-methyl-CoA-racemase (AMACR)-negative pseudohyperplastic variant of adenocarcinoma in CS. To the best of our knowledge, there have been no published case reports of this variant in CS till date. An accurate diagnosis is essential as this uncommon, aggressive cancer has limited therapeutic options.

Fertility preservation in young patients' with cancer.

Preservation of fertility is an important issue in the management of young cancer patients. Though embryo cryostorage is a well-established procedure, it can only be availed by couples. Recent studies have indicated increasing success rates with mature and immature oocyte cryopreservation. Cryostorage induces injuries on the human oocytes which can be minimized by slow freezing and vitrification. Selection of candiidates is crucial so that the most suitable technique can be offered without any delay in initiation of cancer therapy. Factors affecting suitability are age of patient, assessment of ovarian reserve, hormonal status and type and stage of neoplastic disease. Encouraging results have been obtained with oocyte in vitro maturation (IVM) followed by vitrification for cryostorage. Data on the use of vitrified eggs in routine in vitro fertilization (IVF) show that pregnancy rates can be comparable to those achieved with fresh oocytes.

The Diagnostic Role of the Marginal Vacuoles in FNAC of Solitary Thyroid Nodules.

CONTEXT: FNAC thyroid is more sensitive as well as specific in segregating neoplastic and non-neoplastic thyroid lesions. Identification of predominant cell pattern, cell morphology and background details in FNAC smears play an important role in categorisation of various thyroid lesions with accuracy. Marginal vacuoles (MVs) have been described as irregular cytoplasmic vacuoles with largely unstained central area. MVs, although suggestive of thyrotoxicosis, are non-specific, as they are also encountered in non- toxic goitre, Hashimoto's thyroiditis and follicular carcinoma. This cytologic finding therefore deserves further study to precisely delineate its utility. Aims & Objective: To investigate whether MVs have a diagnostic role in FNAC of solitary thyroid nodule Setting & Design: This study was conducted on 40 patients who presented with solitary thyroid nodule. METHODS & MATERIAL: Forty patients having solitary thyroid nodule were subjected to FNAC on an outpatient basis. Their cytomorphological features were studied with special attention to presence of MVs. MVs if present were then graded as no/ scant (gradeI ), moderate (gradeII) and abundant (gradeIII). RESULTS AND CONCLUSION: Majority (77.5%) of nodular goitres had insignificant MVs (gradeI) in their smears. Significant MVs (gradeII+III) were limited to autoimmune thyroiditis presenting as solitary nodule and follicular neoplasms. Abundant MVs/ gradeIII were seen in follicular neoplasm only. MVs were not present in rest of neoplastic goitres. This implies that MVs are a marker of follicular differentiation.

A study on the biochemical and the morphological changes in the liver in renal transplant recipients with an evidence of the HBV and the HCV infections.

CONTEXT: Renal transplantation is the definitive treatment in renal failure patients. Liver disease is a known problem in renal transplant recipients. They may be consequent to immunosuppression, drug toxicity, altered immune response to viruses and hemodialysis. AIMS: The aim of this study was to analyze and correlate the biochemical parameters and histopathology of liver biopsy among renal transplant recipients with both HBV and HCV infection and to correlate them. SETTING: The study group had thirty cases. Enrolment criteria included coinfection with HBV and HCV ; elevated liver enzymes and recipient of renal allograft. There was acontrol group of ten patients who were HBC and HCV positive but had not undergone renal transplant. MATERIAL & METHODS: Liver function tests including alkaline phosphatase, SGOT, SGPT and serum bilirubin levels were donet. Percutaneous liver biopsies were carried out using Menghini's needle.. Stains done included hematoxylin and eosin (H & E), vanGieson, reticulin and Perl's stain. Histopathological grading was performed using Metavir scoring system. Immunohistochemistry (IHC) was done where required for ground glass hepatocytes. Correlation of SGOT, SGPT and Alkaline phosphatase of the study group and the controls was carried out with the grading. STATISTICAL ANALYSIS: Statistical tests done included paired "t" test at 5% and test of probability. RESULTS: There was no statistically significant correlation between the controls and the transplanted patients. It was concluded that serum enzyme levels could be used to predict histological grade in the control group but not in the transplant recipients (p>0.05).